This application proposes to create an innovative Center of Biomedical Research Excellence (COBRE) focused on the Comparative Biology of Tissue Repair, Regeneration and Aging. Tissue regeneration in mammals is extremely limited. However, robust regeneration is the norm for countless lower vertebrates and invertebrates. In addition, nature has endowed diverse animals with remarkable longevity and robust tissue repair mechanisms that slow aging-induced degenerative processes. The COBRE research theme uniquely focuses on using diverse non-mammalian and mammalian model organisms together with comparative biology approaches to address several overarching and fundamental questions in the field of regenerative biology that can only be addressed at the level of the whole organism. This research focus represents a cornerstone of the long term strategic scientific Vision of the Mount Desert Island Biological Laboratory (MDIBL), and builds on the MDIBL and Maine INBRE success stories and on MDIBL's longstanding and increasingly important expertise in comparative biomedical research. The four proposed COBRE projects have extensive points of intersection and interaction and focus on defining mechanisms of limb and sensory axon regeneration in zebrafish, the impact of aging and somatic mutation load on mouse hematopoietic stem cell tissue homeostasis, and the effects of aging and stress on zebrafish tissue regeneration. Proposed scientific cores will provide essential services and resources to Project Leaders and will be valuable to a larger scientific community. The Comparative Animal Models Core will provide COBRE investigators with resources necessary to utilize diverse non-mammalian animal models in regenerative and aging biology research. The Comparative Functional Genomics Core will provide data management and analysis expertise to COBRE investigators. It will also develop a novel web-based resource that integrates data generated by COBRE investigators with published data sets in order to provide a systems-level view of regeneration that will inform new hypotheses about how genes regulate regenerative responses in diverse organisms. The Administrative Core will provide administrative, scientific, and fiscal leadership; implement a career development plan for junior faculty that facilitates their transition to independence; and implement an evaluation strategy to assess the progress of the COBRE in accomplishing its goals. The proposed COBRE will greatly enhance MDIBL's growth and development, which in turn will contribute to the continued growth and enhancement of the biomedical research infrastructure in Maine.